Selection of potential targets for stratifying congenital pulmonary airway malformation patients with molecular imaging: is MUC1 the one?

Currently there is a global lack of consensus about the best treatment for asymptomatic congenital pulmonary airway malformation (CPAM) patients. The somatic KRAS mutations commonly found in adult lung cancer combined with mucinous proliferations are sometimes found in CPAM. For this risk of developing malignancy, 70% of paediatric surgeons perform a resection for asymptomatic CPAM.

CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy.

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation.

Multimodal image-guided surgery of HER2-positive breast cancer using [In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast tumor model.

Background: Combining modalities using dual-labeled antibodies may allow preoperative and intraoperative tumor localization and could be used in image-guided surgery to improve complete tumor resection. Trastuzumab is a monoclonal antibody against the human epidermal growth factor-2 (HER2) receptor and dual-labeled trastuzumab with both a fluorophore (IRDye800CW) and a radioactive label (In) can be used for multimodal imaging of HER2-positive breast cancer. The aim of this study was to demonstrate the feasibility of HER2-targeted multimodal imaging using [In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast cancer model.

Evaluation of integrin αvβ cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer.

Photoacoustic clinical imaging.

Photoacoustic is an emerging biomedical imaging modality, which allows imaging optical absorbers in the tissue by acoustic detectors (light in - sound out). Such a technique has an immense potential for clinical translation since it allows high resolution, sufficient imaging depth, with diverse endogenous and exogenous contrast, and is free from ionizing radiation. In recent years, tremendous developments in both the instrumentation and imaging agents have been achieved.

Detection of visually occult metastatic lymph nodes using molecularly targeted fluorescent imaging during surgical resection of pancreatic cancer.

Background: Although most patients with PDAC experience distant failure after resection, a significant portion still present with local recurrence. Intraoperative fluorescent imaging can potentially facilitate the visualization of involved peritumoral LNs and guide the locoregional extent of nodal dissection. Here, the efficacy of targeted intraoperative fluorescent imaging was examined in the detection of metastatic lymph nodes (LNs) during resection of pancreatic ductal adenocarcinoma (PDAC).

Recommendations for reporting on emerging optical imaging agents to promote clinical approval.

Intraoperative fluorescence imaging is particularly well-suited for surgical applications due to its inherently high sensitivity, resolution, and ability to provide images in real-time. To date, the intraoperative observation of fluorescence has largely been subjective. With the need to show objective evidence in order to demonstrate the benefit of this technique, quantitative data needs to be provided to overseeing regulatory bodies.

Correction to: ASO Author Reflections: Fluorescent-Guided Surgery to Augment Pancreatic Cancer Surgery.

In the original version of this article, George A. Poultsides's middle initial was incorrect.

Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence.

For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for imaging during resection. However, for cancers with difficult imaging conditions, surgical value may lie in tumor mapping of surgical specimens.

Advances in Diagnostic and Intraoperative Molecular Imaging of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. To improve outcomes, there is a critical need for improved tools for detection, accurate staging, and resectability assessment. This could improve patient stratification for the most optimal primary treatment modality.

Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging.

Background: Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon.

First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800.

Introduction: Maximizing extent of surgical resection with the least morbidity remains critical for survival in glioblastoma patients, and we hypothesize that it can be improved by enhancements in intraoperative tumor detection. In a clinical study, we determined if therapeutic antibodies could be repurposed for intraoperative imaging during resection.

Methods: Fluorescently labeled cetuximab-IRDye800 was systemically administered to three patients 2 days prior to surgery.

Development and Preclinical Validation of a Cysteine Knottin Peptide Targeting Integrin αvβ6 for Near-infrared Fluorescent-guided Surgery in Pancreatic Cancer.

Intraoperative near-infrared fluorescence (NIRF) imaging could help stratification for the proper primary treatment for patients with pancreatic ductal adenocarcinoma (PDAC), and achieve complete resection, as it allows visualization of cancer in real time. Integrin αvβ6, a target specific for PDAC, is present in >90% of patients, and is able to differentiate between pancreatitis and PDAC. A clinically translatable αvβ6-targeting NIRF agent was developed, based on a previously developed cysteine knottin peptide for PET imaging, R01-MG, and validated in preclinical mouse models.

Selection of optimal molecular targets for tumor-specific imaging in pancreatic ductal adenocarcinoma.

Discrimination of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) or peritumoral inflammation is challenging, both at preoperative imaging and during surgery, but it is crucial for proper therapy selection. Tumor-specific molecular imaging aims to enhance this discrimination and to help select and stratify patients for resection. We evaluated various biomarkers for the specific identification of PDAC and associated lymph node metastases.

Regulatory Aspects of Optical Methods and Exogenous Targets for Cancer Detection.

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval.

Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery.

Purpose: The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.

Procedures: The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)-score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma.

Results: Integrin αβ, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.